The Rad17 homologue of Arabidopsis is involved in the regulation of DNA damage repair and homologous recombination
The Rad17 homologue of Arabidopsis is involved in the regulation of DNA damage repair and homologous recombination
复制标题
DOI：
10.1111/j.1365-313x.2004.02097.x
复制
发表时间：
2004-06-01
期刊：
影响因子：
7.2
通讯作者：
Puchta, H
中科院分区：
文献类型：
--
作者：
Heitzeberg, F;Chen, IP;Puchta, H
RAD17参与酵母和人类细胞的DNA检查点控制。该基因的同源物以及该途径的其他基因(9-1-1复合体)存在于拟南芥中，并与酵母和人类的同源基因共享保守的序列结构域。DNA损伤剂可在转录水平上诱导AtRAD17。AtRAD17突变体对DNA损伤化学物质博莱霉素和丝裂霉素C(MMC)的敏感性增加，这种敏感性可以通过互补来逆转，这表明Rad17功能的丧失扰乱了植物细胞的DNA修复。我们的结果进一步被9-1-1复合体(Rad9)的一个突变体的表型所证实，该突变体也对相同的化学物质敏感。AtRAD9和AtRAD17似乎是上位性的，因为双突变体并不比单个突变体对化学物质更敏感。突变体显示双链断裂(DSB)的一般修复延迟。然而，染色体内同源重组(HR)的频率增加。然而，这些突变体精通于通过基因毒性胁迫进一步诱导HR。我们的结果表明，突变的Rad17途径与DNA修复的全面解除调控有关，这似乎与非同源DSB修复的缺陷有关。
Rad17 is involved in DNA checkpoint control in yeast and human cells. A homologue of this gene as well as other genes of the pathway (the 9-1-1 complex) are present in Arabidopsis and share conserved sequence domains with their yeast and human counterparts. DNA-damaging agents induce AtRAD17 transcriptionally. AtRAD17 mutants show increased sensitivity to the DNA-damaging chemicals bleomycin and mitomycin C (MMC), which can be reversed by complementation, suggesting that the loss of function of Rad17 disturbs DNA repair in plant cells. Our results are further confirmed by the phenotype of a mutant of the 9-1-1 complex (Rad9), which is also sensitive to the same chemicals. AtRAD9 and AtRAD17 seem to be epistatic as the double mutant is not more sensitive to the chemicals than the single mutants. The mutants show a delay in the general repair of double-strand breaks (DSBs). However, frequencies of intrachromosomal homologous recombination (HR) are enhanced. Nevertheless, the mutants are proficient for a further induction of HR by genotoxic stresses. Our results indicate that a mutant Rad17 pathway is associated with a general deregulation of DNA repair, which seems to be correlated with a deficiency in non-homologous DSB repair.